This contract supports the identification of human B cell epitopes derived from Borrelia bugdorferi, coupled with basic studies to understand protective immunity mediated by antibodies, as well as pathological consequences of antibody responses. Milestones include 1) epitope identification; 2) epitope validation that must include in vitro evaluation using human samples; 3) submission of epitope data, computer software, and structural data to the Immune Epitope Database and Analysis Resource; and 4) studies to help understand the mechanisms of protection or pathogenesis elicited by antibodies associated with the newly identified epitopes. This contract will produce comprehensive human B cell epitope maps of three antigens, OspA, OspC and DbpA, from Borrelia burgdorferi, the causative agent of Lyme disease. The contractor will produce libraries of OspA, OpsC and DbpA human monoclonal antibodies (HuMAbs) from Lyme disease patients and characterize the HuMAbs for functional activities associated with protective immunity. Antibody cross-reactivities to human host antigens will also be investigated, as prior studies reveal potential associations between antibody responses to some components of the pathogen and the debilitating, autoimmune-like disease symptoms associated with Lyme Disease. Results of the proposed contract will contribute to development of Lyme disease diagnostics, vaccines, and immunotherapies.